The renaissance of gene therapy

January 10, 2017 Constantine Theodoropulos


Gene therapy and gene editing are at the beginning of a renaissance, according to speakers at Biotech Showcase 2017. While sizeable challenges exist, they are being overcome, leaving the field able to exploit potentially large opportunities.

This state of the industry is spurring renewed interest from investors and commercialization partners, moderator Chris Von Seggern, partner at ClearView Healthcare Partners, points out.

“We’re seeing efficacy data that indicates gene therapy and gene editing approaches can do what more established therapeutics can’t,” explains Jonathan Ellis, VP and head, science licensing and technology licensing, and worldwide business development, GlaxoSmithKline. This will have a big impact on difficult diseases.

Promising data is spurring excitement after years of retrenching in response to significant safety issues and some patient deaths. Only six years ago, “there was a moratorium on gene therapy and no one knew what genome editing really meant,” recalls Curt Herberts, senior VP and chief business officer, Sangamo Therapeutics. As the technology has been derisked, however, conversations with potential partners have become more constructive, he says. “Now companies want to differentiate gene therapy from other therapies to provide maximum benefit to patients.”

Differentiation is both a carrot and stick. Companies with new, significantly more effective therapies jeopardize the revenue streams of less innovative drug developers, catalyzing them to think more innovatively about their product pipelines.

Successes mount

In May 2016, GlaxoSmithKline received approval from the European Commission to use Strimvelis, an ex-vivo stem cell gene therapy, to treat the extremely rare condition of severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID). “This isn’t a home run, but we got to first base,” Ellis says.

“Our task now is to take this approval to other areas,” he continues. There are no lessons here that can be broadly applied by the field, though. Ellis emphasizes that each group of regulators, particularly in this space, can view the world quite differently from one another. “The field is very complicated. The problems won’t be solved in the abstract, but rather by companies bringing products forward in different therapeutic areas and geographies, testing the best methods to bring them to patients. “There’s so much to do in this field before it achieves its potential across a slew of diseases. Ultimately, gene therapy will find its place alongside other therapeutics.”

Challenges remain

Successes like these are heartening, but significant challenges remain before widespread commercialization is achieved.

“Eliminating batch-to-batch variability, for instance, doesn’t make headlines, but resolving the manufacturing issues is absolutely essential for commercialization,” Ellis stresses. Scalability is an issue, too. Developers must think about the production process very early so that the process for the first-in-human trials remains the same as it is scaled-up. Eliminating, or at least minimizing, process changes in scale-up provides the continuity regulators expect and, therefore, minimizes regulatory risks.

At the scientific level, panelists cited challenges in tightening targeted delivery, combating the immune response, dealing with cell turnover and packaging, and identifying related applications that allow current work to advance into other areas. “As we understand the biology and how to use the technologies, we can address the challenges step-by-step to bring gene therapies to more applications while we continue to solve the issues,” Lesley Stolz, head, JLABS California, comments.

Monogenic diseases are the low-hanging fruit that helps companies achieve results while tackling those issues. By targeting diseases with single point mutations, clinical success and commercialization becomes more likely in the short term. Spark Therapeutics is taking that approach.

Spark Therapeutics just received FDA approval to amend its orphan drug designation for voretigene neparvovec to include all inherited retinal diseases caused by biallelic RPE65 mutations. “This represents an important change in the way the agency is thinking,” says Dan Faga, chief business officer.

Sangamo Therapeutics, in contrast, is focused on the gene editing technology. Its objective is to be able to target any base pair, eliminate off-target effects and ensure significant on-target activity. Its approach relies on its zinc finger technology. One of this technology’s attractions is that it only requires a transient delivery system, which allows Sangamo to invest in non-viral delivery technology.

For gene therapies, the next level of innovation must involve tools. As Matthew Kane, CEO, Precision BioSciences, says, “We targets our therapies to the liver and the eye. We are confident we can deliver adeno-viral vectors to those organs, but can we deliver them to the muscle, lung or for central nervous system disease? Those targets are just out of reach for current technologies. That will be the next wave of innovation.”

 Investor interest is strong

“The environment for capital has been strong the past four to five years, with the exception of a few months in 2016,” Faga says. “Companies in the AV and CAR-T field are well-funded, and a number of programs are entering the clinic,” which further stimulates investment. “There’s a lot of innovation and a long way to go.”

Ultimately, durability and value will build a strong industry sector. Five years from now, the panelists predict, the gene therapies will have expanded applications to treat more conditions, and more and larger companies will be involved.



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